11
Differential Diagnosis of Differential Diagnosis of Neoplastic Pancreatic Cysts:Neoplastic Pancreatic Cysts:The Role of EUS with Guided The Role of EUS with Guided
FNAFNA
E.M.Santo,Y.Ron,O.Barkay,Y.Kopelman,M.Leshno,S.Marmor
Dep. of Gastroenterology & Hepatology,
Dep.of Pathology
Tel-Aviv Sourasky Medical Center
22
IntroductionIntroduction
Cystic lesions constitute about 10 % Cystic lesions constitute about 10 % of pancreatic tumorsof pancreatic tumors
Significant increase in detection Significant increase in detection due due
to widespread use of US,CT to widespread use of US,CT
Most lesions discovered incidentallyMost lesions discovered incidentally
33
Clinical PresentationClinical Presentation
AsymptomaticAsymptomatic
Abdominal painAbdominal pain
JaundiceJaundice
PancreatitisPancreatitis
44
Clinical PresentationClinical Presentation
AsymptomaticAsymptomatic
Ca in situ / invasive cancer – 17%Ca in situ / invasive cancer – 17%
Lesion with malignant potentialLesion with malignant potential – – 42%42%
Fernandez Del Castillo et al. Arch Surg 2003
55
ClassificationClassification
Non neoplasticNon neoplastic (pseudocysts) (pseudocysts)
NeoplasticNeoplastic
Mucinous
Non Mucinous
66
ClassificationClassification
Non Mucinous CystsNon Mucinous Cysts
1.1. Serous cystadenomaSerous cystadenoma
2.2. Cystic endocrine tumorsCystic endocrine tumors
3.3. OtherOther
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ClassificationClassification
Mucinous CystsMucinous Cysts
1.1. Mucinous cystadenomaMucinous cystadenoma
2.2. Malignant mucinous cystic Malignant mucinous cystic tumorstumors
3.3. Intraductal papillary mucinous Intraductal papillary mucinous neoplasms - IPMNneoplasms - IPMN
88
99
DiagnosisDiagnosis
CT – microcystic appearance, centralCT – microcystic appearance, central fibrosis- fibrosis- SerousSerous Unilocular, macrocystic, peripheralUnilocular, macrocystic, peripheral calcification- calcification- MucinousMucinous
MRCPMRCP – – MPD dilatation, mural nodulesMPD dilatation, mural nodules ductal connection - IPMNductal connection - IPMN
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DiagnosisDiagnosis
EUS - highly sensitiveEUS - highly sensitive
FNA – fluid characteristics, FNA – fluid characteristics, tumor markers, cytologytumor markers, cytology
CEA in fluid - most accurate CEA in fluid - most accurate markermarker
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EUS – Serous cystEUS – Serous cyst
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EUS – Mucinous cystEUS – Mucinous cyst
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AIMAIM
Evaluation of the various Evaluation of the various parameters parameters (clinical,morphological,fluid (clinical,morphological,fluid content, cytology) and their content, cytology) and their contribution to the ability to contribution to the ability to distinguish between distinguish between serous serous and and mucinousmucinous cystic tumors cystic tumors
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AIMAIM
Validation of the current Validation of the current criteria used to distinguish criteria used to distinguish between various cystic between various cystic tumors (gold standard based tumors (gold standard based on surgical pathology )on surgical pathology )
Establishing new criteria Establishing new criteria with higher sensitivity and with higher sensitivity and specificityspecificity
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AIMAIM
Provide an algorithm for Provide an algorithm for the diagnosis and the diagnosis and treatment of pancreatic treatment of pancreatic cystic lesionscystic lesions
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Heuristics used in our Heuristics used in our InstituteInstitute for Dx of for Dx of SerousSerous
cystscysts
- Clinical Clinical - Microcystic morphologyMicrocystic morphology- CEA level CEA level < 5 ng / ml< 5 ng / ml- Histology- cuboidal, non Histology- cuboidal, non
secreting cellssecreting cells
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- ClinicalClinical- Morphology – unilocular, thick Morphology – unilocular, thick
septa, solid componentsepta, solid component- High viscosity (mucinous) High viscosity (mucinous)
fluidfluid- CEA - CEA - >140 ng/ml>140 ng/ml- Histology – columnar Histology – columnar
secreting epitheliumsecreting epithelium
Heuristics used in our Heuristics used in our InstituteInstitute for Dx of Mucinous for Dx of Mucinous
cystscysts
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MethodsMethods
1919
MethodsMethods
Retrospective study Retrospective study 170 patients between 1977-170 patients between 1977-
20062006 155 patients ,195 EUS exams155 patients ,195 EUS exams 40 patients – EUSx2 or more40 patients – EUSx2 or more 101 women, 54 men101 women, 54 men Mean age – 64.3Mean age – 64.3±14 years±14 years
2020
MethodsMethods
Demographic dataDemographic data Clinical presentationClinical presentation Imaging – US, CT , EUSImaging – US, CT , EUS FNAFNA Surgical findingsSurgical findings Follow up on all patients (Follow up on all patients (office visits , office visits ,
data from family physicians, data from family physicians, gastroenterologists, patient’s families)gastroenterologists, patient’s families)
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MethodsMethods
EUSEUS Cyst location, size, morphologyCyst location, size, morphology FNA – fluid:FNA – fluid:
- characteristics- characteristics
- cytology- cytology
- tumor markers –- tumor markers –CEA,CA19-9,CA72-4,MCA CEA,CA19-9,CA72-4,MCA
Cyst wall sampling (cell block)Cyst wall sampling (cell block)
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Results
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ResultsResults
Clinical PresentationClinical Presentation No.No. %%
Incidental finding 103103 69.369.3
Abdominal pain 2929 19.619.6
Weight lossWeight loss 2 2 1.41.4
JaundiceJaundice 2 2
1.41.4
Abdominal pain/weight lossAbdominal pain/weight loss 55 3.43.4
DyspepsiaDyspepsia 22 1.4 1.4
DiarrheaDiarrhea 2 2 1.41.4
Diarrhea/weight lossDiarrhea/weight loss 33 2.02.0
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ResultsResultsLocation No. %
Head 52 33.5
Neck 14 9.0
Body 41 26.5
Tail 25 16.1
Other 23 14.8
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– 37 patients had surgery with histological findings.
– 140 patients had FNA but results were available for 80 patients.
Results
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ResultsResults
Surgical Pathology No. %
Non neoplastic 6 16.2Serous 4 10.8 Mucinous 13 35.1Mucinous ca. 11 29.7IPMN 2 5.4Neuroendocrine 1 2.7
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ResultsResults
FNA Histology No. %
Non neoplastic 12 16.0Serous 27 33.8 Mucinous 25 31.3Carcinoma 14 17.5Neuroendocrine 2 2.5
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– 32 patients had both FNA and surgical biopsy.
– The agreement rate was 66% of the cases regarding mucinous vs. non-mucinous with kappa=0.33.
– Sensitivity and specificity of FNA are 59% and 80% respectively.
EUS-FNA vs. Surgical biopsy
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ResultsResults Mean of Ln(CEA)Mean of Ln(CEA)** levels were 2.6 and levels were 2.6 and
5.8 for non mucinous and mucinous 5.8 for non mucinous and mucinous cases respectively (p<0.0001)cases respectively (p<0.0001)
No statistically significant difference No statistically significant difference with all the other tumor markers with all the other tumor markers testedtested
Rate of solid component in cyst – the Rate of solid component in cyst – the difference was not statistically difference was not statistically significant (p=0.14)significant (p=0.14)
No difference concerning cyst size or No difference concerning cyst size or morphologymorphology*CEA is highly skewed distributed and therefore we *CEA is highly skewed distributed and therefore we transformed the CEA level to Ln(CEA)transformed the CEA level to Ln(CEA)
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10
Class
12.00
10.00
8.00
6.00
4.00
2.00
0.00
-2.00
lnC
EA
Mucinous
Ln
(CEA
) BoxPlot
Non-mucinous
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95% C.I.for OR
Variable B S.E.
p-value OR Lower Upper
log10CEA 1.818 0.727 0.012 6.2 1.48 25.6
Age -0.041 0.022 0.06 0.96 0.92 1.01
Logistic regression results
Note that CA-19 is highly correlated with CEA, and when CEA levels are unavailable the CA-19 level should play a role in the diagnostic process.
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1.00.80.60.40.20.0
1 - Specificity
1.0
0.8
0.6
0.4
0.2
0.0
Sensi
tivi
ty
ROC Curve
ROC of CEA classification of Mucinous vs. Serous
1-specificity
sen
sit
ivit
y
AUC=0.902 (CI=(0.79-1.0))
A Threshold of CEA=58
ng/ml yields 86.4% and
87.5% sensitivity
and specificity
respectively
A Threshold of CEA=58
ng/ml yields 86.4% and
87.5% sensitivity
and specificity
respectively
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ConclusionsConclusions EUS is a useful tool but it can not EUS is a useful tool but it can not
alonealone distinguish between cystic distinguish between cystic lesions with variable malignant lesions with variable malignant potential potential
EUS-FNA EUS-FNA alonealone is also limited in is also limited in its ability to correctly diagnose a its ability to correctly diagnose a cystic lesion – sensitivity 59% cystic lesion – sensitivity 59% specificity 80%specificity 80%
CombinationCombination of parameters – of parameters – cytology and CEA levels (or CA cytology and CEA levels (or CA 19-9 levels) can significantly 19-9 levels) can significantly increase the diagnostic yieldincrease the diagnostic yield
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A Practical Decision Algorithm based on
the Threshold Decision Model
Source: NEJM 1980; 302:1109-17
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For a patient with a pancreatic cyst there are several management options:For a patient with a pancreatic cyst there are several management options:
• Wait and watch approach with a follow up.
• An initial EUS-FNA is performed and patients with increased cyst fluid CEA or positive cytology undergo a surgical resection.
• Surgical resection of all cysts without prior EUS evaluation.
• Wait and watch approach with a follow up.
• An initial EUS-FNA is performed and patients with increased cyst fluid CEA or positive cytology undergo a surgical resection.
• Surgical resection of all cysts without prior EUS evaluation.
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Beside the preferences of the patient, the following parameters are relevant to the decision process:
Beside the preferences of the patient, the following parameters are relevant to the decision process:
• Age of the patient 60 year• 61-75 year• > 75 year
• Co-morbidity status (CV diseases, diabetes, other neoplastic diseases)
• No co-morbidity
• Co-morbidity
• Test results (CT, EUS)
• Age of the patient 60 year• 61-75 year• > 75 year
• Co-morbidity status (CV diseases, diabetes, other neoplastic diseases)
• No co-morbidity
• Co-morbidity
• Test results (CT, EUS)
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0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
2005200320012000199919981997year
0
10
20
30
40
50
60
70
80
90
Cy
st
siz
e (
mm
)
CEA in cyst
CA19-9 in blood
Cyst size
Natural history of mucinous cystic neoplasm 78 years old woman with incidental finding - 1977
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Age
<=60 60 - 75 >75
Co-morbidity Yes YesNo No
Positive Cytology or CEA>60
Yes No Yes No
5< CEA<60
Compliance
= Surgical Resection
= Wait and Watch
Complexity of Surgical resection
Yes No
Yes No
Yes No
= Debate
Yes No
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Age
<=60 60 - 75 >75
Co-morbidity Yes YesNo No
Positive Cytology or CEA>60
Yes No
= Surgical Resection
= Wait and Watch
Complexity of Surgical resection
Yes No
= Debate
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Age
<=60 60 - 75 >75
Co-morbidity Yes No
Positive Cytology or CEA>60
Yes No
= Surgical Resection
= Wait and Watch
Yes No
= Debate
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Thank You